CONTEXT:Oestrogens play an important protective role on the vascular system. The endothelial cell layer is a direct target for these hormones, and expresses at least two oestrogen receptors, ER-alpha and ER-beta. Recent studies have shown that vascular healing is significantly modulated by circulating bone marrow-derived cells. A subset of these stem cells, endothelial progenitor cells (EPCs), have recently been described as a population of pluripotent cells within the peripheral blood capable of differentiating into endothelial cells. OBJECTIVE:In the present study we investigated the expression of ER-alpha and ER-beta on human EPCs and the effect that oestrogens have on the function of EPCs in vitro. METHODS:EPCs were isolated and cultured from healthy donors. RT-PCR, western blotting and immunohistochemistry were used to assess expression of ER-alpha and ER-beta. Proliferation and CFU assays were used to assess the response of EPCs to different doses of 17,beta-oestradiol. MAIN OUTCOME MEASURES:Expression of ER-alpha and ER-beta in EPCs, and the effect of 17,beta-oestradiol on proliferation of EPCs. RESULTS:Human EPCs express ER-alpha mRNA and protein. 17,beta-oestradiol increases proliferation of EPCs and CFU in a dose-dependent manner. CONCLUSIONS:Human EPCs express ER-alpha but not ER-beta, and oestrogens can stimulate the proliferation of these cells in vitro. Oestrogens exert these effects at concentrations that are usually reached during stimulation for in vitro fertilization in women, and therefore further studies are needed to clarify the clinical significance of these effects.

译文

背景:雌激素对血管系统起重要的保护作用。内皮细胞层是这些激素的直接靶标,并表达至少两种雌激素受体,即ER-α和ER-β。最近的研究表明,循环的骨髓来源的细胞显着地调节了血管的愈合。这些干细胞的一个子集,内皮祖细胞(EPC),最近被描述为能够分化为内皮细胞的外周血中的多能细胞群。
目的:在本研究中,我们研究了ER-α和ER-β在人EPC上的表达以及雌激素在体外对EPC功能的影响。
方法:从健康供体中分离并培养EPC。 RT-PCR,蛋白质印迹和免疫组化被用于评估ER-alpha和ER-beta的表达。增殖和CFU分析用于评估EPC对不同剂量的17-β-雌二醇的反应。
主要观察指标:EPCs中ER-α和ER-β的表达,以及17-β-雌二醇对EPCs增殖的影响。
结果:人EPCs表达ER-αmRNA和蛋白。 17,β-雌二醇以剂量依赖性方式增加EPC和CFU的增殖。
结论:人类EPCs表达ER-α而不表达ER-β,并且雌激素可以刺激这些细胞的体外增殖。雌激素以刺激女性体外受精时通常达到的浓度发挥这些作用,因此需要进一步的研究以阐明这些作用的临床意义。

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